Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection: a randomised study
| Autor: | Paul J. Thuluvath, Paul Y. Kwo, Harvey A Tatum, John M. Vierling, Paul J. Pockros, Stanislas Pol, Fiona McPhee, Megan Wind-Rotolo, Ola Weiland, Nina Weis, Philip D. Yin, William Sievert, Eric Hughes, Gideon M. Hirschfield, Maribel Rodriguez-Torres, Eric Lawitz, Vinod K. Rustgi, Stephen D. Shafran, Mark S. Sulkowski, Stefan Zeuzem, Gamal Esmat, Marc Bourlière, Gregory T. Everson, Dennis Hernandez, Lawrence Serfaty, Zhaohui Liu, Imam Waked, Wayne Ghesquiere, Michael W. Fried, Steven Schnittman, Maurizia Rossana Brunetto, Stephanie Noviello, Christophe Hézode, Norbert Bräu |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male medicine.medical_specialty Daclatasvir Pyrrolidines Adolescent Genotype Peginterferon-alfa Placebo Gastroenterology Drug Administration Schedule law.invention Polyethylene Glycols Therapy naive chemistry.chemical_compound Young Adult Randomized controlled trial Double-Blind Method law Internal medicine Ribavirin Medicine Humans Adverse effect Aged business.industry Remission Induction Imidazoles virus diseases Interferon-alpha Valine Hepatitis C Chronic Middle Aged Viral Load digestive system diseases Recombinant Proteins Treatment Outcome chemistry Immunology Drug Therapy Combination Female Carbamates business medicine.drug |
| Zdroj: | Gut. 64(6) |
| ISSN: | 1468-3288 |
| Popis: | To evaluate the safety and efficacy of daclatasvir, an HCV NS5A inhibitor with pangenotypic activity, administered with peginterferon-alfa-2a/ribavirin.In this Phase 2b double-blind, placebo-controlled study, treatment-naive adults with HCV genotype 1 (N=365) or 4 (N=30) infection were randomly assigned (2:2:1) to daclatasvir 20 mg or 60 mg, or placebo once daily plus weekly peginterferon-alfa-2a and twice-daily ribavirin. Daclatasvir recipients achieving protocol-defined response (PDR; HCV-RNAlower limit of quantitation at Week 4 and undetectable at Week 10) were rerandomised at Week 12 to continue daclatasvir/peginterferon-alfa-2a/ribavirin for 24 weeks total duration or to placebo/peginterferon-alfa-2a/ribavirin for another 12 weeks. Patients without PDR and placebo patients continued peginterferon-alfa/ribavirin through Week 48. Primary efficacy endpoints were undetectable HCV-RNA at Weeks 4 and 12 (extended rapid virologic response, eRVR) and at 24 weeks post-treatment (sustained virologic response, SVR24) among genotype 1-infected patients.Overall, eRVR was achieved by 54.4% (80/147) of genotype 1-infected patients receiving daclatasvir 20 mg, 54.1% (79/146) receiving 60 mg versus 13.9% (10/72) receiving placebo. SVR24 was achieved among 87 (59.2%), 87 (59.6%), and 27 (37.5%) patients in these groups, respectively. Higher proportions of genotype 4-infected patients receiving daclatasvir 20 mg (66.7%; 8/12) or 60 mg (100.0%; 12/12) achieved SVR24 versus placebo (50.0%; 3/6). A majority of daclatasvir-treated patients achieved PDR and experienced less virologic failure and higher SVR24 rates with a shortened 24-week treatment duration. Adverse events occurred with similar frequency across all treatment groups.The combination of daclatasvir/peginterferon-alfa/ribavirin was generally well tolerated and achieved higher SVR24 rates compared with placebo/peginterferon-alfa/ribavirin among patients infected with HCV genotype 1 or 4.NCT01125189. |
| Databáze: | OpenAIRE |
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